The primary goal of the Cellular Kinetics Section is to achieve a better understanding of the kinetic behavior of normal and tumorous tissues and to use such information to design optimal forms of chemotherapy. Toward this end both animal studies and studies of patients have been undertaken. This year, alterations in DNA synthesis induced by chemotherapy in normal and tumorous murine tissues have been completed and results have been published. Cellular kinetics studies in an ovarian carcinoma murine tumor model have been completed and accepted for publication this year. Pharmacokinetics of intraperitoneal administration of methotrexate and adriamycin have been related to cellular kinetics, tissue penetration and systemic toxicity for the first time. Other animal studies include: The kinetics effects of tamoxifen followed by estrogen, tamoxifen or estrogen alone have been studied in DMBA induced breast cancer in Sprague-Dawley rats. The tumors are studied by autoradiography, TdR incorporation, and flow cytometry. No evidence of recruitment or synchronization with estrogen, following tamoxifen occurred at 1,2, or 3 days post-therapy. This experiment is being repeated, using a different time schedule, to look for evidence of recruitment following hormonal therapy. Studies are proceeding with cultured murine melanomas (Cloudman CCL-53, IA and Mel) and human melanomas (FCC-1 and HM-1) to look for melatonin-receptors and responsivity to MSH as measured by increased tyrosinase production.